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Published on: July 14, 2016
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[Study on the relationship between human cytidine deaminase gene polymorphisms and Ara-C sensitivity]
Xiao-wen Chen1, Li-jie Yue, Cheng-rong Li
1Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi
|November 28, 2008
Summary
Genetic variations in the cytidine deaminase (CDA) gene were identified in childhood acute leukemia patients. The 208A genotype shows increased sensitivity to cytosine arabinoside (Ara-C) therapy.
Area of Science:
- Pharmacogenomics
- Molecular Biology
- Oncology
Context:
- Childhood acute leukemia (AL) treatment often involves cytosine arabinoside (Ara-C).
- Individual responses to Ara-C can vary significantly.
- Genetic factors influencing drug metabolism and efficacy are crucial for personalized medicine.
Purpose:
- To investigate the association between coding single-nucleotide polymorphisms (cSNPs) in the human cytidine deaminase (CDA) gene and Ara-C sensitivity in childhood AL.
- To characterize the functional impact of CDA variants on enzyme activity and drug response.
Summary:
- Three known CDA cSNPs (79A/C, 208G/A, 435T/C) were identified in a Chinese population with childhood AL.
- The 208A allele exhibited significantly reduced deamination activity for Ara-C compared to the 208G allele.
- Yeast transformants expressing the 208A variant showed increased sensitivity to Ara-C, indicated by a lower IC50 value.
Impact:
- Identifies a potential pharmacogenetic marker (CDA 208A genotype) for predicting Ara-C response in childhood AL.
- Provides a molecular basis for understanding variable Ara-C sensitivity.
- May inform future therapeutic strategies for acute leukemia by enabling genotype-guided treatment selection.
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